Oxarane-Acrylate System to Double the Clinical Service Life of Restorative Resins Abstract: In order to develop a novel restorative system with at least twice the lifetime of Bis-GMA/TEGDMA- based composites, their incomplete cure and susceptibility to hydrolysis and esterase degradation must be overcome. To address these problems, we will develop a novel superhydrophobic, degradation-resistant, dental restorative based on an Oxirane/Acrylate interpenetrating network System (OASys, pronounced Oasis). These novel monomers based on fluoridated urethanes with either dioxirane or diacrylate functionality can be highly converted to form a hydrophobic, degradation-resistant, tough and resilient interpenetrating polymer network (IPN) that is inherently highly crosslinked. By their nature, these characteristics impart low residual stresses, high resistance to hydrolytic and enzymatic degradation, and biocompatibility. We will also develop a novel one-step (primer-less), smart, antimicrobial bonding resin with in situ-generated, colorless and color stable, silver nanoparticles (AgNPs). The bonding resin will contain a phosphate group plus both oxirane and acrylate functionalities. The oxirane and acrylate functionalities bond to the corresponding functionalities in the IPN resin matrix for potentially a much stronger bond than the conventional methacrylate system. The phosphate group will allow the bonding resin to wet etched mineral surfaces as well as bond directly to calcium in Ca-phosphate mineral structures. In the event of marginal gap formation, the smart in situ-generated AgNPs will release Ag+ ions and create an antibacterial environment, thereby further reducing the incidence of recurrent caries. Five specific aims are proposed: 1. To determine the effect of using oxiranes, increased hydrophobicity, and IPNs on resin mechanical properties, physical properties and in vitro biocompatibility. The more promising compositions will be combined with reinforcing filler and used for Aim 2. 2. To determine the effect of using a 4- Phospho-NPG GA oxirane (4POA)-based bonding system and in situ-generated silver nanoparticles (AgNP) on bonding resin mechanical properties, physical properties, and in vitro biocompatibility and antibacterial activity, as well as on bond strength to oxirane/acrylate interpenetrating network composites.. The two best- performing composites will be chosen for subsequent aims. 3. To determine the effect of using oxiranes, increased hydrophobicity, and IPNs on resin resistance to the oral biochemical environment. The two best- performing groups chosen in Aim 2 will be fatigue- and wear-tested after exposure to acidic, basic and esterase-containing environments for 90 days. 4. To determine the effect of using oxiranes, increased hydrophobicity, and IPNs on resin resistance to bacterial degradation. The two best-performing groups from Aim 2 will be tested in an artificial mouth bacterial biofilm model. 5. To determine the in vivo biocompatibility of the OASys. The best performing OASys will be tested in three in vivo biocompatibility models: delayed-type hypersensitivity, oral mucosa irritation, and pulp and dentin response tests. 1